PXD021413-1

PXD021413 is an original dataset announced via ProteomeXchange.

Title	Inflammatory Signaling is Regulated by Fucosylation in Metastatic Breast Cancer Cells
Description	N-linked glycosylation results in a large branched tree-like sugar structure composed of several types of individual carbohydrates being attached to a protein. Fucosylation is one specific type of glycosylation that is defined by the addition of α-L-fucose to a carrier protein. Although fucosylation has been relatively well defined as a biomarker for progression in some human cancers, for example, pancreatic and hepatocellular carcinoma, its role in breast cancer is much less well defined. A growing body of evidence indicates that levels of fucosylation correlate with breast cancer progression and contributes to metastatic disease. However, very little is known about the signaling and functional outcomes that are driven by fucosylation. We performed tandem- mass-tag (TMT) proteomics on 4T1 metastatic mammary tumor cells that were treated with a fucosylation inhibitor, 2-fluorofucose (2FF) or vehicle (DMSO) control. This analysis identified >400 proteins that were significantly increased or decreased in 2FF treated samples compared to the DMSO treated samples. We found that two proteins, Tollip and Bcl-10, were downregulated in 4T1 cells in response to 2FF treatment. Functionally, Tollip and Bcl10 signaling induce pro-inflammatory responses through activation of NF-κB, a transcription factor that is pro-tumorigenic and a prime target in human cancer. Our results show that treatment of 4T1 cells with 2FF leads to a reduction in NF-κB expression and activity through increased IκBα. This observation is consistent with a reduction in inflammatory response due to the loss of Tollip and Bcl-10 expression. Collectively, our results indicate that fucosylation is a key mediator of inflammatory signaling in metastatic breast cancer cells.
HostingRepository	PRIDE
AnnounceDate	2020-12-21
AnnouncementXML	Submission_2020-12-21_03:53:32.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD021413
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Emma Doud
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2020-09-10 23:07:54	ID requested
⏵ 1	2020-12-21 03:53:32	announced

Dataset with its publication pending

submitter keyword: fucosylation

N-glycsoylation

breast cancer, metastasis, NF-κB

Elizabeth Yeh
contact affiliation	Associate Professor of Pharmacology & Toxicology, Indiana University School of Medicine, Indianapolis, IN
contact email	esyeh@iu.edu
lab head
Emma Doud
contact affiliation	Indiana University School of Medicine
contact email	edoud@iu.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD021413
     1. Label: PRIDE project
     2. Name: Inflammatory Signaling is Regulated by Fucosylation in Metastatic Breast Cancer Cells